Transcription
Hello, my name is Le Polovski, and I'm director of psoriasis and phototherapy service in Rapid Medical Center and clinical associate professor Dermatology and Television University in Israel. I'm really excited to spend the next 10 minutes talking about psoriasis and inflammatory bowel disease, the overlapping pathways, and treatment considerations. These are my disclosures of conflicts of interest.
Presentation content: We will start talking about psoriasis and IBD pathophysiology and mutual risk factors. Then, we will discuss treating confirmative biologics in a patient with psoriasis and then treatment of psoriasis in a patient with IBD. And in the end, we will discuss multi-tumor necrosis factor alpha-induced skin diseases.
So, regarding mutual risk factors, we know from many different genome-wide association studies that IBD and psoriasis share common genetic logins involving pathways of interleukin-23. As you can see here in this recently published meta-analysis, we can see the estimated prevalence of inflammatory bowel disease in patients with psoriasis. And as you can see, the most common association is having psoriasis in Crohn's disease patients. It is less common in UC patients. And regarding quite a square association of sort of IBD and psoriasis patients, it is also relatively common, and again, Crohn's disease is more common in patients, as well as the whole target qualities.
So, summarizing this epidemiological data, we can conclude that the most common situation is to have psoriasis imitation for Crohn's disease. What about pathophysiology? And in this nice, recently published in the Journal of Internal Medicine, we can see that both diseases start with apparent antigen presentation in an impaired mucosal barrier in case of IBD, and probably antigen coming from keratinocytes or melanocytes in case of psoriasis. As you probably know, in both diseases, dendritic cells are involved, and the key, then one of the most important cytokines here is TNF. And as we know, treatments against TNF are widely used for both diseases. And our immunological pathway involved in both diseases are T helper cells and their cytokines, and the interleukin-23. And medications targeting interleukin-23 are again both used in involved diseases. But also, we know that IL-17, which is a product of pathogenic T helper 17 cells, and it's important in disease, but not really in IL-17 is working on psoriasis, but harmless in inflammatory bowel disease, and probably showing us that the interleukin-17 has a positive or physiological role in the bowel, and we will discuss it a little bit later.
So, to treat IBD in a patient with psoriasis, we should consider what our existing treatments for IBD and what influence they may have on their psoriasis. So, it is still what they use in treatment, mainly in the field of hematology, and this is nothing to do with psoriasis. Corticosteroids, systemic or corticosteroids, as we know, we don't use psoriasis. Corticosteroids, but it is used by our rheumatology colleagues to treat psoriatic arthritis in some situations. Topical corticosteroids, of course, are widely used medications in psoriasis also. And next, systemic treatments here, azathioprine, 6-mercaptopurine, but still what we use in gastroenterology. And talking about patients with psoriasis, we should consider the possible risk for non-melanoma skin cancers and using these treatments, especially in combination with phototherapy for psoriasis, which should be avoided. So, this is the consideration for these medications. And for infliximab and adalimumab, they have nothing to do with psoriasis. And methotrexate, as we all know, it's still widely used in treating patients with psoriasis, and especially with psoriatic arthritis. Sulfasalazine, we also use in psoriasis, usually it's a bridge treatment and some special situations. And cyclosporine is not widely used in psoriasis.
So, regarding biologics used and approved to treat psoriasis, infliximab, adalimumab, ustekinumab, and secukinumab are all used for psoriasis. Infliximab and adalimumab are used while before IBD, maybe still are the first-line biologics for IBD. As I mentioned before, ustekinumab is used from 2009 to treat psoriasis and is also approved for IBD. And the next group of medications is IL-17 inhibitors, and very recently approved in Europe and in Israel, being secukinumab, which is still not approved by the FDA. All these medications are very effective medications for skin disease and for psoriatic arthritis, but all are contraindicated or at least awareness should exist for prescribing them to patients with IBD because it was shown previously that they may exaggerate IBD, and these medications will not be a good choice for patients having IBD. And to treat the psoriasis, our consideration, we should think about prescribing biologics for psoriasis patients with IBD is the dosage because for all these medications, dosages used for IBD are much higher than for psoriasis. So, if you want to prescribe this medication for a patient with psoriasis who also has IBD, and we want him to have benefit from the IBD point of view, we should use appropriate dosage. And then this is again a good reason to collaborate with gastroenterologists.
And what about TNF and IBD-induced skin diseases? In this very nice review recently published in Lancet, it was proposed that we can classify psoriasis according to pathophysiology in three groups, like classic psoriasis mainly driven by IL-17, paradoxical psoriasis mainly driven by interferon, and future psoriasis driven by IL-36. So, treating patients with skin diseases associated with TNF is one of my special topics of interest, and we work in cooperation with the IBD unit in our institution. And this paper was published in Annals of Internal Medicine a couple of years ago, and summarizing a very large cohort of almost 1,000 patients with IBD, and more than 200 of them developed skin lesions. And these findings actually reflect also our experience. And it is important to know that the median time for the development of skin lesions was 1.9 years. It's not unusual to see patients starting suffering from a skin lesion induced by TNF two, three years after initiation of the therapy. And it is relatively common here, it's almost 30% of patients, and of course, different degrees of severity.
And what about the clinical presentation? Because previously called paradoxical psoriasis, but I think that it is inappropriate to use this term because most of these patients, their rash, their skin disease is surrounded from dermatitis and not actually psoriasis, even from the clinical hypothetical point of view, and immunological, as I mentioned before. And in this cohort, 30% of patients did have this psoriasiform eczema, and only 5% palmoplantar psoriasis, which is relatively common in the different population of patients, patients suffering from rheumatological diseases, and for example, rheumatoid arthritis, predictive anti-TNF. So, in this population, palmoplantar psoriasis, but in IBD patients, it's regularly uncommon. And true psoriasis, I mean, it's interstitial psoriasis or the novel true psoriasis is also really relatively uncommon. So, the most common dermatitis lesions typically developed facial, rational, genitalia, and scalp. And as you understand, these lesions are very common for psoriasis. I mean, this is one of the reasons in the past we called it paradoxical psoriasis or paradoxical brand skin disease. And physical scalp is a special site, and I will discuss it in a bit later. And then here you can see examples of skin lesions from this paper and Annals of Internal Medicine, and the common sense of environment, and again, the morphology of secondary infection. And this picture is of inflammatory or pressure because anti-TNF inducing plan revolution. And the special clinical form of scalp involvement in these patients causing kind of pressure and severe inflammation of the scalp, as you can see here on the storage, you can see the psoriasis and the mixed inflammatory interest rate environment, also hair follicles, and miniaturization of the hair follicles explaining their location. And it should be noted in all cases, we have treated almost 20 patients with this disease, and this is reversible after discontinuation of treatment.
So, how to manage patients of IBD suffering from anti-TNF and use skin lesions? And this is in our core publishing Journal of Componentis recently with 180 patients. And their main findings were that scar location was independently associated with less remission of skin lesion, and that early switch of offending biologic was independently associated with a higher probability of remission of stimulants. Actually, it was also our conclusion that this is a paper we published recently. And what we found that when you have patients with skin eruption induced by anti-TNF, first, we should decide if there is a civilian inflammatory or official or not. Because in the patients with severe inflammatory eruption, it is mandatory to switch the biologic to another group. In our case, it was a stellar, but these days, there are a number of medications available. And in the case of dermatitis without inflammatory patient, there is a probability to keep anti-TNF. The offending culprit may be different. And because it's, you probably know, this is something that's very important to the patients from the IBD point of view. So, not always in case of skin eruption only, it is necessary to switch biological, but in cases of inflammatory eruption, and it is very important and as soon as possible.
This clinical team, I would like to summarize and to thank you for your attention.